Radiation Therapy with or without Cetuximab in Treating Patients Who Have Undergone Surgery for Locally Advanced Head and Neck Cancer

Basic Trial Information

Phase

Type

Status

Age

Trial IDs

Phase III

Supportive care, Treatment

Active

18 and over

RTOG-0920NCI-2011-00878, CDR0000651536, NCT01311063, NCT00956007

Trial Description

Summary

This randomized phase III trial studies radiation therapy alone to see how well it works compared with radiation therapy and cetuximab in treating patients who have undergone surgery for head and neck cancer that has spread to nearby tissues or organs. Radiation therapy uses high-energy x-rays to kill tumor cells. Using a 3-dimensional (3-D) image of the tumor to help focus the radiation directly onto the tumor, and giving the radiation in higher doses over a shorter period of time, may kill more tumor cells and cause fewer side effects. Monoclonal antibodies, such as cetuximab, may block tumor growth by targeting certain cells. It is not yet known whether radiation therapy is more effective when given alone or together with cetuximab in treating patients with head and neck cancer that has been removed by surgery.

Further Study Information

PRIMARY OBJECTIVES:

I. Test whether the addition of cetuximab to radiation therapy will improve overall survival (OS) in postoperative patients with intermediate risk following surgery.

SECONDARY OBJECTIVES:

I. Assess the impact of the addition of cetuximab to postoperative radiation therapy on disease-free survival (DFS).

II. Assess the impact of the addition of cetuximab to postoperative radiation therapy on acute dysphagia, dry mouth, skin toxicity, and other toxicities (Common Terminology Criteria for Adverse Events [CTCAE], version [v.] 4) and their relationships to patient-reported outcomes at 3 months.

III. Assess the impact of the addition of cetuximab to postoperative radiation therapy on late dysphagia, dry mouth, skin toxicity, and other toxicities (CTCAE, v. 4) and their relationships to patient-reported outcomes at 12 and 24 months.

V. Tumor analysis of human papillomavirus (HPV) infection (as defined by in situ hybridization), specifically, within the cohort of patients with oropharynx cancer, to perform an exploratory analysis of the impact of HPV on DFS and OS in this patient subset.

I. Assess the impact of the addition of cetuximab to postoperative radiation therapy on local-regional control.

II. Assess the impact of the addition of cetuximab to postoperative radiation therapy on patient-reported quality of life (QOL), swallowing, xerostomia, and skin toxicity based on head and neck specific instruments, including the Performance Status Scale for Head and Neck Cancer (PSS-HN), the Functional Assessment of Cancer Therapy-Head & Neck (FACT-H&N), the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS), and the Dermatology Life Quality Index (DLQI).

III. Assess the impact of the addition of cetuximab to postoperative radiation therapy on cost-utility analysis using the EuroQol (EQ-5D).

IV. To evaluate the utility of image-guided radiotherapy (IGRT) as a means of enhancing the efficacy (i.e., local-regional control) of intensity-modulated radiation therapy (IMRT) while reducing the acute and/or late toxicity (particularly xerostomia) and improving patient-reported outcomes (particularly XeQOLS scores).

V. To retrospectively compare the local regional control rate for patients treated with IMRT alone (no IGRT or cetuximab) with similar patients treated with external beam radiotherapy alone in the postoperative trial Radiation Therapy Oncology Group (RTOG) 95-01.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo IMRT once daily (QD) for a total of 30 fractions in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo IMRT as in arm I. Patients also receive cetuximab intravenously (IV) over 60-120 minutes once weekly beginning at least 5 days prior to the start of IMRT for 11 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 1 and 3 months, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Clinical stage T1, N1-2 or T2-4a, N0-2, M0 including no distant metastases, based upon the following minimum diagnostic workup:

General history and physical examination by a radiation oncologist and/or medical oncologist within 8 weeks prior to registration

Examination by an ear, nose and throat (ENT) or head & neck surgeon, within 8 weeks prior to registration; a laryngopharyngoscopy (mirror and/or fiberoptic and/or direct procedure) is recommended but not required

Chest x-ray (at a minimum) or chest computed tomography (CT) scan (with or without contrast) or CT/positron emission tomography (PET) of chest (with or without contrast) within 8 weeks prior to registration

Gross total resection of the primary tumor with curative intent must be completed within 7 weeks of registration with surgical pathology demonstrating one or more of the following “intermediate” risk factors:

Close margin(s) of resection, defined as cancer extending to within 5 mm of a surgical margin, and/or an initially focally positive margin that is subsequently superseded by intraoperative negative margins; similarly, patients whose tumors had focally positive margins in the main specimen but negative margins from re-excised samples in the region of the positive margin are eligible; for questions or ambiguities about an individual case, contact Dr. Machtay and/or Dr. Holsinger prior to enrolling the patient

Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; noninvasive cancers (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible) are permitted even if diagnosed and treated < 3 years ago; patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with primary tumor (T)1-2, nearby lymph nodes (N)0, metastasis (M)0 resected differentiated thyroid carcinoma, who are eligible

Per the operative and/or pathology report, positive margin(s) (defined as tumor present at the cut or inked edge of the tumor), nodal extracapsular extension, and/or gross residual disease after surgery; note: patients whose tumors had focally positive margins in the main specimen but negative margins from re-excised samples in the region of the positive margin are eligible; for questions or ambiguities about an individual case, contact Dr. Machtay and/or Dr. Holsinger prior to enrolling the patient

Prior systemic chemotherapy or anti-EGF therapy for the study cancer; note: prior chemotherapy or anti-EGF therapy for a different cancer is allowable

Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields

Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration

Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration

Idiopathic pulmonary fibrosis or other severe interstitial lung disease that requires oxygen therapy or is thought to require oxygen therapy within 1 year prior to registration

Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol

Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note: human immunodeficiency virus (HIV) testing is not required for entry into this protocol; protocol-specific requirements may also exclude immuno-compromised patients

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